A study of clofarabine combination therapy for infant ALL

JRCT ID: jRCTs041190043

Registered date:17/06/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Infant acute lymphoblastic leukemia
• Date of first enrollment: 28/06/2019
• Target sample size: 42
• Study type: Interventional

Intervention(s)

MLL-rALL(HR): PSL pretreatment(1week) ->Induction therapy R ->Early intensification R(CLARA) ->Interim intensification R(MARMA) ->Re-induction R-I(MAVDAD) ->(Re-induction R-II) ->HSCT(Hematopoietic Stem Cell Transplantation)

MLL-rALL(IR): PSL pretreatment (1week) ->Induction therapy R ->Early intensification R(CLARA) ->Interim intensification R(MARMA) ->Re-induction R-I(MAVDAD) ->Re-induction R-II(CLARA) ->maintenance R

MLL-gALL(LR): PSL pretreatment(1week) ->Induction therapy G ->Early intensification G ->Intensification G-I ->Intensification G-II ->Re-induction G ->maintenance G-I ->maintenance G-II

Outcome(s)

• Primary Outcome: 3 year event free survival (EFS) rate of MLL rearranged infant ALL

Secondary Outcome

(1) Any Grade 5 toxicity (CTCAE ver 4.0)
(2) Adverse events occurring during CLARA (Clofarabine and cytarabine chemotherapy) treatment phase which delay more than 4 weeks of next chemotherapy
(3) Unacceptable grade 4 severe toxicity during CLARA treatment phase
(4) Hematological CR rate and MRD positive rate of timepoint 2 and timepoint 3
(5) Remission rate after induction chemotherapy
(6) Time to treatment failure
(7) Overall survival period
(8) Event free survival (EFS)
(9) Cumulative recurrence rates
(10) Non-relapse mortality
(11) Positive rate of PCR-MRD, FCM-MRD, and NGS-MRD at each timepoint
(12) Pharmacokinetic (PK) testing of clofarabine in infants
(13) Incidence of clinically relevant toxicities more than grade 3 (CTCAE ver4.0)
(14) Treatment completion rate
(15) Evaluation of quality of life for patients evaluated by families
(16) Complication on 100th day, 1st year, and 2nd year after stem cell transplantation
(17) Incidence of severe RSV infection
(18) Incidence of invasive fungal infection
(19) Incidence of sepsis
(20) Incidence of severe viral infection during maintenance therapy
(21) Immune function during maintenance therapy
(22) Overall survival and event free survival rate according to treatment for patients who showed PCR-MRD positive at TP4
(23) Evaluation of immune function during maintenance therapy (IR)
(24)Evaluation of immune function during maintenance therapy (LR)
(25) Incidence of silent inactivation of L-asparaginase.
(26) OS, EFS and incidence of adverse events related L-asparaginase according to the silent inactivation of L-asparaginase.
(27) Correlation of silent inactivation of L-asparaginase and anti-L-asparaginase antibody.
(28) Correlation between NUDT15 gene polymorphisms and 3-year EFS
(29) Correlation between NUDT15 gene polymorphisms and hematological toxicities (>= grade 3) during maintenancetherapy.

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: <= 1age old
• Gender: Both

Include criteria

A patient must meet all of the following criteria in order to be eligible to participate in MLL-17 study:
(1) Infants less than 365 days of age at time of diagnosis of acute lymphoblastic leukemia (ALL)
(2) Patients with newly diagnosed ALL.
(3) A written informed consent of CHM-14 must be obtained prior to the registration of MLL-17.
(4) A written informed consent of MLL-17 registration must be obtained from the parents or guardians.

Exclude criteria

A patient who meets any of the following criteria will be excluded from participation in MLL-17 study:
(1) If patients are diagnosed at < 30 days of age, patients gestational age is less than 36 weeks and 0 days.
(2) If patients meet any of the following diagnostic criteria:
a. T-ALL
b. Presence of t(9;22) (q34;q11) or BCR-ABL fusion transcript,
c. Presence of t(8;14)(q24;q32), t(2;8)(p13;q24), t(8;22)(q24;q11) or specific fusion transcript associated with mature B-ALL
d.Down syndrome associated ALL
* Mixed phenotype acute leukemia (MPAL), and acute leukemia of ambiguous lineage (AUL) will be included in this clinical trial.
However, the following cases are excluded.
a. Cases in which the myeloblast ratio is higher than that of the lymphoblast
b. Cases which meet the criteria with T-ALL
c. Cases which meet the criteria with lymphoid antigen- positive AML
(3) Patients who evaluated as ECOG Performance status (PS) score 4 which modified for infants.
(4) Patients with unacceptable severe organ failure.
a. Patients with uncontrollable severe cardiac failure
b. Patients with uncontrollable severe renal failure
c. Patients with respiratory failure who require mechanical ventilation
d. Patients with unacceptable severe central nerve system hemorrhage
(5) Patients with uncontrollable severe infection.
(6) Patients with severe congenital disease or unacceptable complications.
(7) Patients with multiple primary cancer.
(8) Patients who received different chemotherapy or radiation therapy before registration.
(9) Patients who evaluated ineligible by principal physician.

Related Information

• Primary Sponsor: Miyamura Takako
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Heart Link Working Project,Gold Ribbom Network,Children's Cancer Association Japan,National Center for Child Health and Development